The growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) form the core of the GH-IGF axis, collectively regulating growth, development, metabolism, and cellular functions.
GH-IGF Axis
The GH-IGF axis serves as the central endocrine system governing human growth, metabolism, and tissue repair. Comprising growth hormone (GH), insulin-like growth factor-1 (IGF-1), and its binding proteins (notably IGFBP-3), this axis operates through a tightly regulated network. GH, secreted by the anterior pituitary gland, is under bidirectional control of hypothalamic growth hormone-releasing hormone (GHRH) and somatostatin, exhibiting pulsatile release patterns (over 70% of daily secretion occurs during deep sleep at night). GH exerts its effects by binding to GHR receptors on hepatocytes, activating the JAK2-STAT5 signaling pathway to stimulate IGF-1 synthesis and secretion. IGF-1, functioning as the primary downstream mediator of GH, forms a ternary complex with IGFBP-3 and acid-labile subunit (ALS), extending its circulatory half-life and facilitating targeted delivery to epiphyseal cartilage, skeletal muscle, and other tissues to mediate GH-induced growth-promoting actions. The GH-IGF axis plays pivotal roles in metabolic regulation, bone health, muscle endurance, inflammatory responses, aging-related changes, and tumorigenesis.
Interactions Among GH, IGF-1, and IGFBP-3
GH, IGF-1, and IGFBP-3 interact within the GH-IGF axis through complex upstream-downstream relationships while maintaining distinct functional profiles:
Growth Hormone (GH)
GH, a 191-amino acid single-chain polypeptide synthesized and secreted by pituitary somatotrophs, is subject to hypothalamic GHRH/somatostatin regulation with pronounced pulsatile secretion (over 70% during nocturnal deep sleep, peaking in adolescence and declining post-maturation). Its biological actions encompass linear bone growth promotion, protein anabolism, and lipolysis induction: GH stimulates hepatic IGF-1 production to indirectly activate chondrocyte proliferation at growth plates, driving pediatric height gain; concurrently, it antagonizes insulin action to elevate blood glucose, enhances fatty acid oxidation for energy, and augments muscle amino acid uptake.
GH deficiency causes pediatric pituitary dwarfism (height <3rd percentile, delayed bone age, metabolic abnormalities), while excess secretion leads to gigantism/acromegaly with elevated cardiovascular risks. Clinical evaluation employs pharmacologic stimulation tests (e.g., insulin tolerance test), with recombinant human GH (rhGH) therapy indicated for GH deficiency (GHD), idiopathic short stature, and adult GHD. Therapeutic monitoring requires serial IGF-1 measurements to optimize dosing and prevent skeletal overgrowth or metabolic complications.
IGF-1
IGF-1, a 70-amino acid single-chain polypeptide sharing ~50% structural homology with proinsulin, is predominantly hepatic-derived but also locally produced in skeletal muscle, cartilage, and adipose tissue. GH-dependent regulation occurs via JAK2-STAT5 pathway activation upon GH-GHR binding, rapidly upregulating IGF-1 transcription with circulating levels peaking within minutes. The 16-24 hour half-life of IGF-1 is significantly prolonged through 90% binding to IGFBP-3 within the ternary complex (IGF-1-IGFBP-3-ALS), regulating bioavailability and tissue targeting.
Dysregulated IGF-1 signaling contributes to oncogenesis through Ras-MEK and PI3K-Akt pathway activation, promoting proliferation and chemotherapy resistance. Therapeutic applications include recombinant human IGF-1 (rhIGF-1) for Laron syndrome and investigational uses in diabetic nephropathy and liver fibrosis.
IGFBP-3
IGFBP-3, the most abundant 264-amino acid IGF-binding protein (29 kDa), contains conserved N-terminal and C-terminal cysteine-rich domains mediating high-affinity IGF-1/IGF-2 binding. Through ALS complexation, it extends IGF half-life while modulating bioactivity. Hepatic synthesis is GH-dependent with pulsatile secretion but stable circulating levels, serving as an indirect GH status marker.
Elevated IGFBP-3 correlates with aggressive cancer phenotypes (pancreatic/colorectal carcinoma), where it promotes lipolysis and inhibits lipogenesis, contributing to cancer cachexia. Serum IGFBP-3 alterations associate with GHD (low levels indicate GH deficiency), diabetes (reduced in insulin resistance), cardiovascular disease (low levels correlate with atherosclerosis), and autoimmune disorders (elevated in rheumatoid arthritis synovial fluid).
Clinical Applications
The GH-IGF-IGFBP-3 panel constitutes the cornerstone for evaluating pediatric growth disorders, guiding therapeutic strategies, and monitoring treatment efficacy. Combined assessment of GH secretory capacity, direct IGF-1 effects, and IGFBP-3 stability provides comprehensive diagnostic insights for short stature, GHD, and therapeutic optimization, serving as an essential endocrine management tool.
New Product Launch: Growth Hormone Triad Antibody Pairs
Stellar Diagnostics introduces premium recombinant rabbit monoclonal antibody pairs for GH, IGF-1, and IGFBP-3, validated for sandwich ELISA and chemiluminescent assays. These reagents offer:
- Ultra-sensitivity for low-abundance analyte detection
- High-affinity binding ensuring assay specificity
- Lot-to-lot consistency for reliable longitudinal monitoring
GH Antibody Pair Recommendations
IGF-1 Antibody Pair Recommendations
IGFBP-3 Antibody Pair Recommendations
